Chiral Switches and Patentability

In the 1990s it was the fashion to change from racemic drugs to single enantiomers with some notable marketing successes being Esomeprazole Escitalopram, Dexketoprofen and Levobupivicaine.  These drugs were originally marketed as racemates and then a “chiral switch” to single enantiomer was carried out, the marketing emphasis being on improvement in desired drug characteristics (potency, efficiency, safety etc).  Patentability was also important.

A recent review article entitled “A Consideration of the Patentability of Enantiomers in the Pharmaceutical Industry in the United States” (Miller C P and Ullrich J P, Chirality, 2008, 20, 762-770) covers some of the chiral switches including a recent patent case involving Ofloxacin and Levofloxacin.  Of course, many generic companies will try to contest the validity of patents relating to single enantiomers on the grounds of obviousness, in view of the prior art on the racemate.  On the other hand, the innovator company will stress the unexpected and superior properties of the enantiomer.  In the case of Ortho-McNeil Pharmaceuticals Inc vs Mylan Laboratories, the surprising fact that Levofloxacin is 10 times more soluble than the racemate, thus conferring favourable properties in the enantiomer, was sufficient for the Court to rule that the enantiomer patent (US 5053 407) was valid.

The article discusses other recent court cases involving racemic switches including two in which Scientific Update consultants have been involved as expert witnesses.  Our consultants have also been involved in court cases involving polymorphism and solvates/hydrates as well as with general process chemistry patents.